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1.
Ther Adv Drug Saf ; 13: 20420986221135931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36420373

RESUMO

Introduction: The primary aim of this study was to compare the incidence of venous thromboembolism (VTE) among women initiating ospemifene vs other selective estrogen receptor modulator (SERM) therapies for estrogen-deficiency conditions or breast cancer prevention, and vs women with untreated vulvar and vaginal atrophy (VVA). The secondary objective examined numerous additional safety outcomes. Methods: This was a retrospective cohort study using the IBM Watson MarketScan claims database. Women receiving ospemifene, another SERM, or with a new diagnosis of VVA with no treatment from 1 May 2013 to 2 October 2018 were followed through the claims for incident adverse outcomes. The primary outcome was the first occurrence of VTE following cohort entry; secondary outcomes included cerebrovascular events and other adverse events potentially associated with SERM use. Cox models compared the risk of VTE between ospemifene and comparators, using a variety of approaches to control for confounding. Results: The incidence of VTE during the first continuous treatment episode was 3.39 (95% confidence interval [CI]: 1.55-6.43) events per 1,000 person-years (PY) for ospemifene (N = 8977), 11.30 (95% CI: 8.81-14.28) events per 1,000 PY for comparator SERM (N = 12,621), and 10.92 (95% CI: 10.49-11.37) events per 1,000 PY for untreated VVA (N = 242,488). Cox models indicated no increase in risk of VTE for ospemifene vs other SERMs (hazard ratio [HR]: 0.40, 95% CI: 0.19-0.82), and vs untreated VVA (HR: 0.47, 95% CI: 0.24-0.91). Conclusion: This real-world safety analysis found no increase in risk of VTE or other adverse events with use of ospemifene in postmenopausal women. Plain Language Summary: Introduction: This study assessed the risk of venous thromboembolism (VTE) among women treated with ospemifene or another selective estrogen receptor modulator (SERM) therapy and women with untreated vulvar and vaginal atrophy (VVA). Numerous additional safety outcomes were examined.Methods: This study was conducted in the IBM Watson MarketScan claims database. Women receiving ospemifene, another SERM, or with a new diagnosis of VVA with no treatment from 1 May 2013 to 2 October 2018 were followed through the claims for adverse outcomes, including VTE, cerebrovascular events (such as stroke), and other outcomes that might occur with use of a SERM. The analyses compared the risk of VTE between ospemifene and the other two groups, using methods that accounted for differences in patient characteristics between the groups. Because few women over 72 years old used ospemifene, the main analyses examined women aged 54-72 years.Results: The analyses included 8,977 ospemifene users, 12,621 other SERM users, and 242,488 women with untreated VVA. Among women aged 54-72 years, only 9 experienced a VTE during ospemifene treatment, while 55 other SERM users and 1,788 women with untreated VVA had a VTE. The analyses that accounted for differences between the groups confirmed that the risk of VTE was no higher in ospemifene users than in either comparison group.Conclusion: This real-world safety analysis found no increase in risk of VTE or other adverse events with use of ospemifene in postmenopausal women.

2.
Cureus ; 14(10): e30346, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36407214

RESUMO

A 76-year-old Japanese man with nephrotic syndrome was admitted to our department for treatment. After his admission, he was administered prednisolone (PSL) at 40 mg/day, and a percutaneous renal biopsy was performed. However, on the first day of admission, his urinary protein decreased from 5.05 g/gCr to 1.85 g/gCr. On the fourth day of admission, his urinary protein further decreased to 0.38 g/gCr and the patient developed acute kidney injury (AKI). Renin-angiotensin system (RAS) inhibitors were suspected to be the cause of AKI; therefore, they were discontinued. After the renal function improved, the urinary protein worsened again to 5.49 g/gCr. Renal pathology suggested minimal change disease (MCD); therefore, PSL was continued. The patient's urinary protein subsequently improved and he had no renal function impairment. Minimal change disease can be complicated by AKI through intravascular volume depletion caused by high urinary protein and hypoalbuminemia. However, when MCD is complicated by RAS inhibitor-associated AKI, the urinary protein may notably decrease, and the patient may present with an atypical course of MCD-associated AKI.

3.
Peptides ; 159: 170901, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36347314

RESUMO

Positive allosteric modulators (PAMs) of G protein-coupled receptors (GPCRs) have drawn attention as novel drug candidates. PAMs can enhance the activities of endogenous agonists which are not only secreted at appropriate times and in parts of the body, but also are immediately metabolized. Therefore, they are expected to show fewer side effects than exogeneous orthosteric ligands. Recently, we have reported that oxytocin (OT) functioned as a PAM of the µ opioid receptor (MOR) which was one of the most potent targets for analgesics. OT is thus thought to be a useful compound for the development of novel analgesics. In this study, several OT analogs were synthesized and evaluated with an intact cell-based assay to investigate the crucial structures of OT for exerting the PAM activity. The assay results indicated that the cyclic structure formed by an intramolecular disulfide bond and the three C-terminal residues containing a small Gly residue of OT were essential for their function as a MOR-PAM. Intriguingly, two analogs having an amide or an ethylene tether instead of the intramolecular disulfide bridge did not have any PAM effects. The results suggested that the disulfide linkage of OT would be a key structure for exerting the PAM activity at the MOR.

4.
Skeletal Radiol ; 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224399

RESUMO

Calcific tendinitis is a potentially symptomatic disorder characterized by calcium deposits in the substance of the tendon. Although this condition can occur in any tendinous tissue throughout the human body, calcium deposition commonly occurs at tendon insertions near the bone-tendon junction. The musculotendinous junction of the deltoid muscle has peculiarly dense intramuscular tendons to which muscle fibers attach obliquely to create muscular strength. Given that the intramuscular tendons themselves, which form the consecutive part from the insertion, are subjected to unpredictable stress load or microtrauma similar to tendon insertions, it is reasonable to assume that calcific tendinitis could also occur at the intramuscular tendons. Here we report a case of chronic symptomatic calcium deposition in the lateral part of the deltoid muscle between the origin and the insertion, which was eventually surgically removed and confirmed as intramuscular calcific tendinitis.

5.
World J Hepatol ; 14(7): 1307-1318, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-36158910

RESUMO

Extracellular vesicles (EVs), especially small EVs (sEVs) derived from liver cells, have been the focus of much attention in the normal physiology and pathogenesis of various diseases affecting the liver. sEVs are approximately 100 nm in size, enclosed within lipid bilayers, and are very stable. The lipids, proteins, and nucleic acids, including miRNAs, contained within these vesicles are known to play important roles in intercellular communication. This mini-review summarizes the application of sEVs. First, liver diseases and the related diagnostic markers are described, and the current active status of miRNA research in diagnosis of hepatocellular carcinoma (HCC) is reported. Second, the biodistribution and pharmacokinetics of sEVs are described, and the liver is highlighted as the organ with the highest accumulation of sEVs. Third, the relationship between sEVs and the pathogenesis of liver disorders is described with emphesis on the current active status of miRNA research in HCC recurrence and survival. Finally, the possibility of future therapy using sEVs from mesenchymal stem (stromal) cells for cirrhosis and other diseases is described.

6.
Sensors (Basel) ; 22(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36080957

RESUMO

Motion capture systems using skin markers are widely used to evaluate scapular kinematics. However, soft-tissue artifact (STA) is a major limitation, and there is insufficient knowledge of the marker movements from the original locations. This study explores a scapular STA, including marker movements with shoulder elevation using upright computed tomography (CT). Ten healthy males (twenty shoulders in total) had markers attached to scapular bony landmarks and underwent upright CT in the reference and elevated positions. Marker movements were calculated and compared between markers. The bone-based and marker-based scapulothoracic rotation angles were also compared in both positions. The median marker movement distances were 30.4 mm for the acromial angle, 53.1 mm for the root of the scapular spine, and 70.0 mm for the inferior angle. Marker movements were significantly smaller on the superolateral aspect of the scapula, and superior movement was largest in the directional movement. Scapulothoracic rotation angles were significantly smaller in the marker-based rotation angles than in the bone-based rotation angles of the elevated position. We noted that the markers especially did not track the inferior movement of the scapular motion with shoulder elevation, resulting in an underestimation of the marker-based rotation angles.


Assuntos
Movimento , Escápula , Fenômenos Biomecânicos , Humanos , Masculino , Amplitude de Movimento Articular , Rotação , Escápula/diagnóstico por imagem , Ombro/diagnóstico por imagem , Posição Ortostática
7.
Hepatol Res ; 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35932481

RESUMO

AIM: Non-alcoholic steatohepatitis (NASH) with fibrosis eventually leads to cirrhosis and hepatocellular carcinoma. Thus, the development of therapies other than dietary restriction and exercise, particularly those that suppress steatosis and fibrosis of the liver and have a long-term beneficial effect, is necessary. We aimed to evaluate the therapeutic effects of the HMGB1 peptide synthesized from box A using the melanocortin-4 receptor-deficient (Mc4r-KO) NASH model mouse. METHODS: We performed short- and long-term administration of this peptide and evaluated the effects on steatosis, fibrosis, and carcinogenesis using Mc4r-KO mice. We also analyzed the direct effect of this peptide on macrophages and hepatic stellate cells in vitro and performed lipidomics and metabolomics techniques to evaluate the effect. RESULTS: Although this peptide did not show direct effects on macrophages and hepatic stellate cells in vitro, in the short-term administration model, we could confirm the reduction of liver damage, steatosis, and fibrosis progression. The results of lipidomics and metabolomics suggested that the peptide might ameliorate NASH by promoting lipolysis via the activation of fatty acid ß-oxidation and improving insulin resistance. In the long-term administration model, this peptide prevented progression to cirrhosis but retained the steatosis state, that is, the peptide prevents the progression to "burnt-out NASH." This peptide inhibited carcinogenesis by about one-third. CONCLUSION: This HMGB1 peptide can reduce liver damage, improve fibrosis and steatosis, and inhibit carcinogenesis, suggesting that the peptide would be a new treatment candidate for NASH and can contribute to the long-term prognosis for patients with NASH.

8.
Insects ; 13(6)2022 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-35735894

RESUMO

Anhydrobiosis, an ametabolic dehydrated state triggered by water loss, is observed in several invertebrate lineages. Anhydrobiotes revive when rehydrated, and seem not to suffer the ultimately lethal cell damage that results from severe loss of water in other organisms. Here, we review the biochemical and genomic evidence that has revealed the protectant molecules, repair systems, and maintenance pathways associated with anhydrobiosis. We then introduce two lineages in which anhydrobiosis has evolved independently: Tardigrada, where anhydrobiosis characterizes many species within the phylum, and the genus Polypedilum, where anhydrobiosis occurs in only two species. Finally, we discuss the complexity of the evolution of anhydrobiosis within invertebrates based on current knowledge, and propose perspectives to enhance the understanding of anhydrobiosis.

9.
R Soc Open Sci ; 9(6): 211371, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35754992

RESUMO

Recently, natural gas (mostly methane) is frequently used as fuel, while hydrogen is a promising renewable energy source. However, each gas produced contains impurity gases. As a result, membrane separation is required. The mixed matrix membrane (MMM) is a promising membrane. The huge surface area and well-defined pore structure of zeolite templated carbon (ZTC)-based MMM allow for effective separation. However, the interfacial vacuum in MMM is difficult to avoid, contributing to poor separation performance. This research tries to improve separation performance by altering membrane surfaces. MMM PSF/ZTC was modified by annealing at 120, 150, and 190°C; coating using 0.01, 0.03, and 0.05 mol tetramethyl orthosilicate (TMOS); and a combination of both, i.e. annealing at 190°C and coating using 0.03 mol TMOS. MMM PSF/ZTC successfully significantly improved CO2/CH4 selectivity by a combination of annealing at 190°C and coating 0.03 mol TMOS from 1.37 to 5.90 (331%), and H2/CH4 selectivity by coating with 0.03 mol TMOS from 4.58 to 65.76 (1378%). The enhancement of selectivity was due to structural changes to the membrane that became denser and smoother, which SEM and AFM observed. In this study, annealing and coating treatments are the methods investigated for improving the polymer matrix and filler particle adhesion.

10.
BMC Genomics ; 23(1): 405, 2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35643424

RESUMO

BACKGROUND: Tardigrades are microscopic animals that are capable of tolerating extreme environments by entering a desiccated state of suspended animation known as anhydrobiosis. While antioxidative stress proteins, antiapoptotic pathways and tardigrade-specific intrinsically disordered proteins have been implicated in the anhydrobiotic machinery, conservation of these mechanisms is not universal within the phylum Tardigrada, suggesting the existence of overlooked components. RESULTS: Here, we show that a novel Mn-dependent peroxidase is an important factor in tardigrade anhydrobiosis. Through time-series transcriptome analysis of Ramazzottius varieornatus specimens exposed to ultraviolet light and comparison with anhydrobiosis entry, we first identified several novel gene families without similarity to existing sequences that are induced rapidly after stress exposure. Among these, a single gene family with multiple orthologs that is highly conserved within the phylum Tardigrada and enhances oxidative stress tolerance when expressed in human cells was identified. Crystallographic study of this protein suggested Zn or Mn binding at the active site, and we further confirmed that this protein has Mn-dependent peroxidase activity in vitro. CONCLUSIONS: Our results demonstrated novel mechanisms for coping with oxidative stress that may be a fundamental mechanism of anhydrobiosis in tardigrades. Furthermore, localization of these sets of proteins mainly in the Golgi apparatus suggests an indispensable role of the Golgi stress response in desiccation tolerance.


Assuntos
Tardígrados , Animais , Peroxidases/genética , Tardígrados/genética , Fatores de Tempo , Transcriptoma , Raios Ultravioleta/efeitos adversos
11.
Jpn J Stat Data Sci ; 5(1): 339-361, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35729993

RESUMO

This study proposes a direction for the utilization of multi-agent simulation (MAS) to consider an optimal prevention strategy for the spread of the coronavirus disease of 2019 (COVID-19) through a pandemic modeling example in Japan. MAS can flexibly express macroscopic phenomena formed through the interaction of micro-agents modeled to act autonomously. The use of MAS can provide a variety of recommendations for bringing a pandemic under control, even in the case of the COVID-19 pandemic, which has become more intense as of 2021. However, models that do not consider individual heterogeneity, such as analytical Susceptible-Exposed-Infectious-Recovered (SEIR) models, are often used as predictive models for infectious diseases and the main reference for decision-making. In this study, we show that by constructing a MAS that simulates a metropolitan city in Japan in a simple manner while considering the heterogeneity of age and other background information, we can capture the effects of various measures such as vaccinations on the spread of infections in a more realistic setting. Moreover, it is possible to offer various recommendations for optimal strategies to suppress a pandemic by combining reinforcement learning with MAS. This study explicates the potential of MAS in the development of strategies to prevent the spread of infection.

13.
JMIR Mhealth Uhealth ; 10(5): e35867, 2022 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-35576560

RESUMO

BACKGROUND: Artificial intelligence-assisted interactive health promotion systems are useful tools for the management of musculoskeletal conditions. OBJECTIVE: This study aimed to explore the effects of web-based video patient education and strengthening exercise therapy, using a mobile messaging app, on work productivity and pain in patients with chronic low back pain (CLBP) receiving pharmacological treatment. METHODS: Patients with CLBP were randomly allocated to either the exercise group, who received education and exercise therapy using a mobile messaging app, or the conventional group. For patient education, a web-based video program was used to provide evidence-based thinking regarding the importance of a cognitive behavioral approach for CLBP. The exercise therapy was developed in accordance with the recommendations for alignment, core muscles, and endogenous activation, including improvement of posture and mobility for proper alignment, stimulation and/or strengthening of deep muscles for spinal stability, and operation of intrinsic pain for the activation of endogenous substances by aerobic exercise. Both groups continued to receive the usual medical care with pharmacological treatment. The end points were changes in work productivity, pain intensity, quality of life, fear of movement, and depression. The observation period for this study was 12 weeks. An analysis adjusted for baseline values, age at the time of consent acquisition, sex, and willingness to strengthen the exercise therapy was performed. RESULTS: The exercise and conventional groups included 48 and 51 patients, with a mean age of 47.9 years (SD 10.2 years; n=27, 56.3% male patients) and 46.9 years (SD 12.3 years; n=28, 54.9% male patients) in the full analysis set, respectively. No significant impact of these interventions on work productivity was observed in the exercise group compared with the conventional group (primary end point: Quantity and Quality method; 0.062 vs 0.114; difference between groups -0.053, 95% CI -0.184 to 0.079; P=.43). However, the exercise group showed consistently better trends for the other end points than did the conventional group. Compared with the conventional group, the exercise group showed a significant improvement in the symptoms of low back pain (3.2 vs 3.8; difference between groups -0.5, 95% CI -1.1 to 0.0; P=.04), quality of life (EuroQoL 5 Dimensions 5 Level: 0.068 vs 0.006; difference between groups 0.061, 95% CI 0.008 to 0.114; P=.03), and fear of movement at week 12 (-2.3 vs 0.5; difference between groups -2.8, 95% CI -5.5 to -0.1; P=.04). CONCLUSIONS: This study suggests that patient education and strengthening exercise therapy using a mobile messaging app may be useful for treating CLBP. This study does not reveal the effect of therapeutic interventions on CLBP on work productivity. Thus, further research is required to assess work productivity with therapeutic interventions. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000041037; https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046866.


Assuntos
Dor Lombar , Aplicativos Móveis , Inteligência Artificial , Terapia por Exercício , Feminino , Humanos , Japão , Dor Lombar/terapia , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Qualidade de Vida
14.
J Orthop Res ; 2022 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-35430725

RESUMO

Although shoulder kinematics have been analyzed by various methods, dynamic shoulder motion is difficult to track. This study aimed to validate the shoulder kinematic analysis using upright four-dimensional computed tomography (4DCT) and to compare the results with optical three-dimensional motion capture. During active elevation, bilateral shoulders of 10 healthy volunteers were tracked using 4DCT and motion capture. The scapulothoracic and glenohumeral rotations and the scapulohumeral rhythm (SHR) at each position were calculated, and the differences between 4DCT and motion capture were compared. During 10-140° of humerothoracic elevation, the scapulothoracic joint showed upward rotation, internal rotation, and posterior tilting, and the glenohumeral joint showed elevation, external rotation, and anterior plane of elevation in both analyses. In scapulothoracic rotations, the mean differences between the two analyses were -2.6° in upward rotation, 13.9° in internal rotation, and 6.4° in posterior tilting, and became significant with humerothoracic elevation ≥110° in upward rotation, ≥50° in internal rotation, and ≥100° in posterior tilting. In glenohumeral rotations, the mean differences were 3.7° in elevation, 9.1° in internal rotation, and -8.8° in anterior plane of elevation, and became significant with humerothoracic elevation ≥110° in elevation, ≥90° in internal rotation, and ≥100° in anterior plane of elevation. The mean overall SHRs were 1.8 in 4DCT and 2.4 in motion capture, and the differences became significant with humerothoracic elevation ≥100°. The 4DCT analysis of in vivo shoulder kinematics using upright computed tomography scanner is feasible, but the values were different from those by skin-based analysis at the elevated arm positions.

15.
NAR Genom Bioinform ; 4(2): lqac029, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35387384

RESUMO

Non-biting midges (Chironomidae) are known to inhabit a wide range of environments, and certain species can tolerate extreme conditions, where the rest of insects cannot survive. In particular, the sleeping chironomid Polypedilum vanderplanki is known for the remarkable ability of its larvae to withstand almost complete desiccation by entering a state called anhydrobiosis. Chromosome numbers in chironomids are higher than in other dipterans and this extra genomic resource might facilitate rapid adaptation to novel environments. We used improved sequencing strategies to assemble a chromosome-level genome sequence for P. vanderplanki for deep comparative analysis of genomic location of genes associated with desiccation tolerance. Using whole genome-based cross-species and intra-species analysis, we provide evidence for the unique functional specialization of Chromosome 4 through extensive acquisition of novel genes. In contrast to other insect genomes, in the sleeping chironomid a uniquely high degree of subfunctionalization in paralogous anhydrobiosis genes occurs in this chromosome, as well as pseudogenization in a highly duplicated gene family. Our findings suggest that the Chromosome 4 in Polypedilum is a site of high genetic turnover, allowing it to act as a 'sandbox' for evolutionary experiments, thus facilitating the rapid adaptation of midges to harsh environments.

16.
ChemMedChem ; 17(17): e202200188, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35393747

RESUMO

Synthetic phosphate-derived functional groups are important for controlling the function of bioactive molecules in vivo. Herein we describe the development of a new type of biocompatible phosphate analog, a fluorophosphoramidate (FPA) functional group that has characteristic P-F and P-N bonds. We found that FPA with a primary amino group was relatively unstable in aqueous solution and was converted to a monophosphate, while FPA with a secondary amino group was stable. Furthermore, by improving the molecular design of FPA, we developed a reaction in which a secondary amino group is converted to a primary amino group in the intracellular environment and clarified that the FPA group functions as a phosphate prodrug of nucleoside. Various FPA-gemcitabine derivatives were synthesized and their toxicity to cancer cells were evaluated. One of the FPA-gemcitabine derivatives showed superior toxicity compared with gemcitabine and its ProTide prodrug, which methodology is widely used in various nucleoside analogs, including anti-cancer and anti-virus drugs.


Assuntos
Neoplasias , Pró-Fármacos , Antivirais/farmacologia , Humanos , Fosfatos , Pró-Fármacos/química , Pró-Fármacos/farmacologia
17.
J Orthop Surg Res ; 17(1): 239, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428333

RESUMO

BACKGROUND: Though alignment of the spine and lower extremities in the standing neutral position has been evaluated, a few studies evaluating the alignment of the upper extremities have also been made. This study assessed the normal alignment of the upper extremities in the standing neutral position and clarified the three-dimensional angular rotations of the upper extremity joints. METHODS: Computed tomography (CT) images of 158 upper extremities from 79 healthy volunteers were prospectively acquired in the standing neutral position using an upright CT scanner. Three-dimensional coordinate systems of the thorax, scapula, humerus, and forearm were designated, and three-dimensional angular rotations of the scapulothoracic, glenohumeral, and elbow joints were calculated. RESULTS: The median angle of the scapulothoracic joint was 9.2° (interquartile range [IQR], 5.2°-12.5°) of upward rotation, 29.0° (IQR, 24.9°-33.3°) of internal rotation, and 7.9° (IQR, 4.3°-11.8°) of anterior tilt. The median angle of the glenohumeral joint was 4.5° (IQR, 0.9°-7.8°) of abduction, 9.0° (IQR, 2.2°-19.0°) of internal rotation, and 0.3° (IQR, - 2.6°-3.1°) of extension. The median angle of the elbow joint was 9.8° (IQR, 6.9°-12.4°) of valgus, 90.2° (IQR, 79.6°-99.4°) of pronation, and 15.5° (IQR, 13.2°-18.1°) of flexion. Correlations in angular rotation values were found between the right and left upper extremities and between joints. CONCLUSIONS: This study clarified the three-dimensional angular rotation of upper extremity joints in the standing neutral position using an upright CT scanner. Our results may provide important insights for the functional evaluation of upper extremity alignment.


Assuntos
Escápula , Articulação do Ombro , Fenômenos Biomecânicos , Voluntários Saudáveis , Humanos , Imageamento Tridimensional/métodos , Amplitude de Movimento Articular , Articulação do Ombro/diagnóstico por imagem , Extremidade Superior/diagnóstico por imagem
18.
Biocontrol Sci ; 27(1): 41-46, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35314559

RESUMO

There are various purification methods have been developed and applied to industrial wastewater with contaminated microorganisms. We previously reported that high-voltage pulsed discharge plasma with cavitation effectively kills Escherichia coli cells. We attempted to expand the application of this disinfection method by using microorganisms such as Bacillus subtilis, Deinococcus radiodurans, and Schizosaccharomyces pombe. These microbial cells were treated with the discharge plasma, and the cell viability, DNA damage, and morphological changes were analyzed to evaluate the bactericidal effect. Interestingly, D. radiodurans, a radio-resistant bacterium showed relatively high sensitivity to the discharge plasma. On the other hand, B. subtilis and S. pombe showed the resistance, showing both sporogenesis. The amount of DNA damage in the treated cells corresponded to the cell viability, but most of the treated cells did not show any morphological changes.


Assuntos
Desinfecção , Água , Bacillus subtilis , Desinfecção/métodos , Escherichia coli/genética
19.
J Phys Chem B ; 126(12): 2361-2368, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35316056

RESUMO

Secretory-abundant heat-soluble (SAHS) proteins, which constitute a protein family unique to tardigrades, are thought to be essential for anhydrobiosis. Our previous study has revealed that one of the SAHS proteins of Ramazzottius varieornatus (RvSAHS1) has a more flexible entrance than a mammalian fatty-acid-binding protein, which has a crystal structure similar to that of RvSAHS1. Recently, SAHS paralogs that are expressed abundantly and specifically in the early embryos of this tardigrade and Hypsibius exemplaris have been identified. Comparing these amino-acid sequences with that of RvSAHS1, we have found characteristic differences as I113F and D146T. In this study, we investigate I113F and D146T mutants' properties of RvSAHS1 using molecular dynamics simulations and compare the structures and fluctuations of their entrances with those of the wild type. The two mutants exhibit different properties at the entrance of the ß-barrel structure. The I113F mutant tends to close the entrance more than the wild type due to the enhanced hydrophobic network inside the cavity. The D146T mutant, in contrast to the I113F mutant, tends to open the entrance. The mechanism by which this mutation opens the entrance is also discussed. Even though only a single mutation located far from the entrance is added to the wild type, there is a clear difference in the tendency to open and close the ß-barrel entrance. It indicates that the entrance properties of the SAHS protein are sensitive to the amino-acid sequence.


Assuntos
Tardígrados , Sequência de Aminoácidos , Animais , Temperatura Alta , Mamíferos/metabolismo , Proteínas/metabolismo , Tardígrados/genética , Tardígrados/metabolismo
20.
PLoS One ; 17(2): e0262892, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35157707

RESUMO

Mesenchymal stem cells (MSCs), which are isolated from adipose tissue (AD-MSCs), umbilical cord (UC-MSCs), or bone marrow, have therapeutic potential including anti-inflammatory and immunomodulatory activities. It was recently reported that MSCs are also effective as a therapeutic treatment for neuropathic pain, although the underlying mechanisms have yet to be resolved. Therefore, in this study, we investigated the effects of human AD- and UC-MSCs on neuropathic pain and its mechanisms using rat models of partial sciatic nerve ligation (PSNL). AD- or UC-MSCs were intravenously administered 4 days after PSNL. Antinociceptive effects were then evaluated using the von Frey and weight-bearing tests. We found that, 3-9 days after the administration of AD- or UC-MSCs to PSNL-exposed rats, both the mechanical threshold and differences in weight-bearing of the right and left hind paws were significantly improved. To reveal the potential underlying antinociceptive mechanisms of MSCs, the levels of activation transcription factor 3- and ionized calcium-binding adapter molecule 1-positive cells were measured by immunohistochemical analysis. AD- and UC-MSCs significantly decreased the levels of these proteins that were induced by PSNL in the dorsal root ganglia. Additionally, UC-MSC significantly improved the PSNL-induced decrease in the myelin basic protein level in the sciatic nerve, indicating that UC-MSC reversed demyelination of the sciatic nerve produced by PSNL. These data suggest that AD- and UC-MSCs may help in the recovery of neuropathic pain via the different regulation; AD-MSCs exhibited their effects via suppressed neuronal damage and anti-inflammatory actions, while UC-MSCs exhibited their effects via suppressed neuronal damage, anti-inflammatory actions and remyelination.


Assuntos
Transplante de Células-Tronco Mesenquimais , Neuralgia/terapia , Neurônios/metabolismo , Fator 3 Ativador da Transcrição/metabolismo , Tecido Adiposo/citologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Gânglios Espinais/imunologia , Gânglios Espinais/metabolismo , Humanos , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Proteínas dos Microfilamentos/metabolismo , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Nervo Isquiático/cirurgia , Cordão Umbilical/citologia
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